The disposition of ethiofos (WR-2721) in the isolated perfused rat liver

We have investigated the disposition of ethiofos (20 mg, 4 microCi [14C]ethiofos) in the isolated perfused rat liver preparation to determine the hepatic contribution to the poor oral bioavailability of the drug. Ethiofos clearance (10.6 +/- 3.3 ml h-1) was only a small fraction (1.2 +/- 0.03%) of the perfusate flow rate. The elimination half-life was calculated at 7.1 +/- 1.9 h. The area under curve, AUC0-4 h, for ethiofos (2858 +/- 314 nM h ml-1) was not significantly different from that of 14C (3038 +/- 692 nM h ml-1) or total material convertible to WR-1065 (total WR-1065, 3324 +/- 612 nM h ml-1), indicating a low level of metabolism. The AUC0-4 h for free WR-1065 (37.5 +/- 23.3 nM h ml-1) was less than 2% of ethiofos. Biliary elimination of ethiofos, WR-1065, and 14C was below 1%. At 4 h postdose, 7.9 +/- 1.9% of the dose of radioactivity remained in the liver. Less than 1.5% could be identified as ethiofos (0.12 +/- 0.09%) or total WR-1065 (1.09 +/- 0.05%). Ethiofos, 14C, and total WR-1065 were approximately evenly distributed between the 10,000-g pellet and supernatant. However, significantly more ethiofos, WR-1065, and 14C were recovered from the 105,000-g supernatant compared with the pellet. In summary, both the metabolism and biliary elimination of ethiofos and its derivatives were sparing. Hence it is likely that in the rat, the contribution of the liver to the presystemic biotransformation and poor bioavailability of ethiofos is relatively minor.     

Cloning of chloroplast psbA and rbcL-genes from cotton Gossipium hirsutum

The fragments of cotton Gossipium hirsutum c.v. 108-f chloroplast genome were cloned in Escherichia coli cells. The cloned psbA and rbcL genes have been selected using the heterologous probes from spinach. The preliminary attempts to clone the complete psbA gene in pUC19 vector failed, probably, due to the toxicity of its product to Escherichia coli cells, and its 5'- and 3'-ends were cloned separately. Reconstruction experiments revealed that while the complete psbA gene was unable to be stably inherited by Escherichia coli cells, its structural part lacking the promoter region could be readily cloned in the bacterial cells.     

Development of the innervation pattern in the upper limb of staged human embryos

The upper limb nerves of 8 human embryos (Carnegie stages 13-21) were studied by reconstruction. In stage 13, upper limb nerves (C5-T1) extended from the spinal cord. In stage 14, these nerves united to form the nascent brachial plexus. In stages 16 and 17, the median nerve, the radial nerve and the ulnar nerve entered into the hand plate. In stages 20 and 21, the upper limb nerves were observed in an orientation and arrangement similar to those in the adult.